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. 2025 Oct:79:101215.
doi: 10.1016/j.yfrne.2025.101215. Epub 2025 Aug 15.

Sex differences in the acute effects of cannabis on human cognition: A systematic review

Justin Matheson  1 , Danial Behzad  1 , Christina Zakala  2 , Thomas Hawken  2 , Bruna Brands  3 , Bernard Le Foll  4 , Christine M Wickens  5 , Anthony C Ruocco  6 , Terri Rodak  7 , Patricia Di Ciano  8
Affiliations

Sex differences in the acute effects of cannabis on human cognition: A systematic review

Justin Matheson et al. Front Neuroendocrinol. 2025 Oct.

Abstract

Acute cannabis exposure can transiently impair cognitive performance, increasing the risk of accidental injury and potentially disrupting activities of daily living. Although sex differences in responses to cannabis have been reported, no systematic review has examined whether these extend to acute cognitive effects. Our primary aim was to examine sex differences in the acute effects of cannabis (including isolated delta-9-tetrahydrocannabinol [THC]) on cognition in humans. Our secondary aim was to determine if sex differences in the acute effects of cannabis vary by cognitive domain, route of administration, or dosing paradigm. Following PRISMA guidelines, we conducted a comprehensive literature search across Embase, MEDLINE, APA PsycInfo, Cochrane Library, and Web of Science databases. Of 1,625 unique records, 169 underwent full-text screening, and 29 studies met inclusion criteria. Six of 29 articles (20.7 %), representing eight of 216 cognitive outcomes (3.7 %), found statistical evidence of sex differences in acute cognitive effects of cannabis/THC. All six found increased effects in female participants in at least one cognitive variable; one study additionally found increased effects in male participants, and one study found divergent cognitive effects in male and female participants. There were no clear patterns by cannabis dosing paradigm, route of administration, or cognitive domain. Overall, we found limited evidence that sex significantly influences the acute cognitive effects of cannabis, though methodological heterogeneity precludes any firm conclusions. Future studies should prioritize the measurement of sex-related factors, such as hormonal modulation of cannabinoid pharmacokinetics and pharmacodynamics.

Keywords: Cannabis; Cognition; Sex differences.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Bernard Le Foll has obtained funding from Indivior for a clinical trial sponsored by Indivior. Dr. Le Foll has in-kind donations of placebo edibles from Indiva. Dr. Le Foll has obtained industry funding from Canopy Growth Corporation (through research grants handled by the Centre for Addiction and Mental Health and the University of Toronto). He has participated in a session of a National Advisory Board Meeting (Emerging Trends BUP-XR) for Indivior Canada and is part of Steering Board for a clinical trial for Indivior. He has been consultant for Shinogi, ThirdBridge, and Changemark. He is part of a scientific advisory board for NFL Biosciences. He got travel support to attend an event by Bioprojet. He is supported by CAMH, Waypoint Centre for Mental Health Care, a clinician-scientist award from the department of Family and Community Medicine of the University of Toronto and a Chair in Addiction Psychiatry from the department of Psychiatry of University of Toronto. Dr. Christine Wickens has served on the Board of Directors for the Canadian Association of Road Safety Professionals and currently serves on the Executive Committee of the International Council on Alcohol, Drugs and Traffic Safety. She also serves on the Canadian Society of Forensic Science’s Drugs and Driving Committee, which acts as an advisory body to the Government of Canada’s Department of Justice with respect to issues of drug impaired driving. No other authors have anything to declare.

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